Local administration of stem cell-derived extracellular vesicles in a thermoresponsive hydrogel promotes a pro-healing effect in a rat model of colo-cutaneous post-surgical fistula

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art_BERGER_Local_administration_of_stem_cellderived_extracellular_vesicles_in_2021.PDF (10.39 MB)
Citações na Scopus
24
Tipo de produção
article
Data de publicação
2021
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ROYAL SOC CHEMISTRY
Autores
BERGER, Arthur
ARAUJO-FILHO, Irami
PIFFOUX, Max
NICOLAS-BOLUDA, Alba
GRANGIER, Alice
BOUCENNA, Imane
REGO, Amalia Cinthia Meneses do
Citação
NANOSCALE, v.13, n.1, p.218-232, 2021
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Extracellular vesicles (EVs), especially from stem/stromal cells (SCs), represent a cell-free alternative in regenerative medicine holding promises to promote tissue healing while providing safety and logistic advantages in comparison to cellular counterparts. Herein, we hypothesize that SC EVs, administered locally in a thermoresponsive gel, is a therapeutic strategy for managing post-surgical colo-cutaneous fistulas. This disease is a neglected and challenging condition associated to low remission rates and high refractoriness. Herein, EVs from a murine SC line were produced by a high-yield scalable method in bioreactors. The post-surgical intestinal fistula model was induced via a surgical cecostomy communicating the cecum and the skin in Wistar rats. Animals were treated just after cecostomy with PBS, thermoresponsive Pluronic F-127 hydrogel alone or containing SC EVs. A PET-monitored biodistribution investigation of SC EVs labelled with Zr-89 was performed. Fistula external orifice and output assessment, probe-based confocal laser endomicroscopy, MRI and histology were carried out for therapy follow-up. The relevance of percutaneous EV administration embedded in the hydrogel vehicle was indicated by the PET-biodistribution study. Local administration of SC EVs in the hydrogel reduced colo-cutaneous fistula diameter, output, fibrosis and inflammation while increasing the density of neo-vessels when compared to the PBS and gel groups. This multi-modal investigation pointed-out the therapeutic potential of SC EVs administered locally and in a thermoresponsive hydrogel for the management of challenging post-surgical colon fistulas in a minimally-invasive cell-free strategy.
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URI
https://observatorio.fm.usp.br/handle/OPI/39434
Referências
  1. Aldaqal SM, 2015, INT SURG, V100, P748, DOI 10.9738/INTSURG-D-14-00120.1
  2. Amrani S, 2008, GASTROEN CLIN BIOL, V32, P946, DOI 10.1016/j.gcb.2008.09.003
  3. Araujo-Filho I., 2016, INDIAN J MED RES PHA, V3, P36
  4. Avalos-Gonzalez J, 2010, WORLD J GASTROENTERO, V16, P2793, DOI 10.3748/wjg.v16.i22.2793
  5. Bala S, 2015, SCI REP-UK, V5, DOI 10.1038/srep10721
  6. Baruah A, 2015, TECH GASTROINTEST EN, V17, P178, DOI 10.1016/j.tgie.2016.02.001
  7. Berger Arthur, 2020, Clin Res Hepatol Gastroenterol, P101474, DOI 10.1016/j.clinre.2020.06.001
  8. Buchanan GN, 2003, DIS COLON RECTUM, V46, P1167, DOI 10.1007/s10350-004-6708-9
  9. Bultmann O, 1998, RES EXP MED, V198, P215, DOI 10.1007/s004330050105
  10. Camussi G, 2010, KIDNEY INT, V78, P838, DOI 10.1038/ki.2010.278
  11. Charoenphun P, 2015, EUR J NUCL MED MOL I, V42, P278, DOI 10.1007/s00259-014-2945-x
  12. Coenen HH, 2017, NUCL MED BIOL, V55, pV, DOI 10.1016/j.nucmedbio.2017.09.004
  13. de Vries F. E. E., 2017, WORLD J SURG, V17, P4224
  14. EL Andaloussi S, 2013, NAT REV DRUG DISCOV, V12, P348, DOI 10.1038/nrd3978
  15. Furuta T, 2016, STEM CELL TRANSL MED, V5, P1620, DOI 10.5966/sctm.2015-0285
  16. Fuster-Matanzo A, 2015, STEM CELL RES THER, V6, DOI 10.1186/s13287-015-0232-9
  17. Galipeau J, 2018, CELL STEM CELL, V22, P824, DOI 10.1016/j.stem.2018.05.004
  18. Galloro G, 2015, WORLD J GASTRO ENDOS, V7, P843, DOI 10.4253/wjge.v7.i9.843
  19. Gatti S, 2011, NEPHROL DIAL TRANSPL, V26, P1474, DOI 10.1093/ndt/gfr015
  20. Girard E, 2014, J VISC SURG, V151, P441, DOI 10.1016/j.jviscsurg.2014.10.004
  21. Gyorgy B, 2015, ANNU REV PHARMACOL, V55, P439, DOI 10.1146/annurev-pharmtox-010814-124630
  22. Hammond J, 2014, J GASTROINTEST SURG, V18, P1176, DOI 10.1007/s11605-014-2506-4
  23. Herrera MB, 2010, J CELL MOL MED, V14, P1605, DOI 10.1111/j.1582-4934.2009.00860.x
  24. Hu L, 2016, SCI REP-UK, V6, DOI 10.1038/srep32993
  25. Hugel B, 2005, PHYSIOLOGY, V20, P22, DOI 10.1152/physiol.00029.2004
  26. Hwang DW, 2015, SCI REP-UK, V5, DOI 10.1038/srep15636
  27. Imai T, 2015, J EXTRACELL VESICLES, V4, DOI 10.3402/jev.v4.26238
  28. Kingham TP, 2009, J AM COLL SURGEONS, V208, P269, DOI 10.1016/j.jamcollsurg.2008.10.015
  29. Klouda L, 2015, EUR J PHARM BIOPHARM, V97, P338, DOI 10.1016/j.ejpb.2015.05.017
  30. Kontzias A, 2012, CURR OPIN PHARMACOL, V12, P464, DOI 10.1016/j.coph.2012.06.008
  31. Kretlow JD, 2007, ADV DRUG DELIVER REV, V59, P263, DOI 10.1016/j.addr.2007.03.013
  32. Kulu Y, 2015, CHIRURG, V86, P311, DOI 10.1007/s00104-014-2848-1
  33. Kumar Nitin, 2013, Gastrointest Endosc Clin N Am, V23, P123, DOI 10.1016/j.giec.2012.10.002
  34. Lai RC, 2011, REGEN MED, V6, P481, DOI [10.2217/rme.11.35, 10.2217/RME.11.35]
  35. Lai RC, 2010, STEM CELL RES, V4, P214, DOI 10.1016/j.scr.2009.12.003
  36. Li N, 2017, INT J NANOMED, V12, P3281, DOI 10.2147/IJN.S134379
  37. Li TF, 2013, STEM CELLS DEV, V22, P845, DOI 10.1089/scd.2012.0395
  38. Liang XT, 2014, CELL TRANSPLANT, V23, P1045, DOI 10.3727/096368913X667709
  39. Liu XL, 2017, NANOSCALE, V9, P4430, DOI 10.1039/c7nr00352h
  40. Lloyd DAJ, 2006, BRIT J SURG, V93, P1045, DOI 10.1002/bjs.5396
  41. Lv KQ, 2019, THERANOSTICS, V9, P7403, DOI 10.7150/thno.32637
  42. Malda J, 2016, NAT REV RHEUMATOL, V12, P243, DOI 10.1038/nrrheum.2015.170
  43. Matanovic MR, 2014, INT J PHARMACEUT, V472, P262, DOI 10.1016/j.ijpharm.2014.06.029
  44. Mauri G, 2017, RADIOL MED, V122, P88, DOI 10.1007/s11547-016-0693-7
  45. Mol EA, 2019, ADV HEALTHC MATER, V8, DOI 10.1002/adhm.201900847
  46. Piffoux M., 2019, [No title captured], Patent No. [WO/2019/002608, 2019002608]
  47. Queern SL, 2017, NUCL MED BIOL, V50, P11, DOI 10.1016/j.nucmedbio.2017.03.004
  48. Quinn M, 2017, WORLD J SURG, V41, P2502, DOI 10.1007/s00268-017-4063-y
  49. Rahmi G, 2016, THERANOSTICS, V6, P739, DOI 10.7150/thno.14064
  50. Ratajczak J, 2006, LEUKEMIA, V20, P1487, DOI 10.1038/sj.leu.2404296
  51. Reis LA, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0044092
  52. Royo F, 2019, NANOSCALE, V11, P1531, DOI 10.1039/c8nr03900c
  53. Sheridan C, 2018, NAT BIOTECHNOL, V36, P212, DOI 10.1038/nbt0318-212a
  54. Silva AKA, 2018, ACS NANO, V12, P9800, DOI 10.1021/acsnano.8b00117
  55. Sukho P, 2018, JOVE-J VIS EXP, DOI 10.3791/57213
  56. Sukho P, 2017, BIOMATERIALS, V140, P69, DOI 10.1016/j.biomaterials.2017.06.011
  57. Swaminath Arun, 2014, World J Gastrointest Pharmacol Ther, V5, P113, DOI 10.4292/wjgpt.v5.i3.113
  58. Tan CY, 2014, STEM CELL RES THER, V5, DOI 10.1186/scrt465
  59. Vader P, 2016, ADV DRUG DELIVER REV, V106, P148, DOI 10.1016/j.addr.2016.02.006
  60. Vosjan MJWD, 2010, NAT PROTOC, V5, P739, DOI 10.1038/nprot.2010.13
  61. Williams Lara J, 2010, Clin Colon Rectal Surg, V23, P209, DOI 10.1055/s-0030-1263062
  62. Xin HQ, 2013, J CEREBR BLOOD F MET, V33, P1711, DOI 10.1038/jcbfm.2013.152
  63. Yeo RW, 2013, J CIRC BIOMARK, V1, P1, DOI 10.5772/57460
  64. Zhang B, 2016, INT J MOL SCI, V17, DOI 10.3390/ijms17020174
  65. Zhang B, 2015, STEM CELLS, V33, P2158, DOI 10.1002/stem.1771
  66. Zhang JY, 2015, J TRANSL MED, V13, DOI 10.1186/s12967-015-0417-0
  67. Zhou Y, 2013, J WATER CLIM CHANGE, V4, P1, DOI 10.2166/wcc.2013.117

Coleções
Artigos e Materiais de Revistas Científicas - FM/Outros
Artigos e Materiais de Revistas Científicas - FM/MDR
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - LIM/43